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Abstract Rice blast, caused by the fungal pathogen Magnaporthe oryzae, is a destructive disease that affects rice (Oryzae sativa L.) on a global scale. Polyamines (PAs) play diverse roles in plant growth and development and responses to biotic and abiotic stimuli. Putrescine (PUT), spermidine (SPD), and spermine (SPM) are the primary forms of polyamines (PAs). In this study, we observed that the accumulation of apoplastic PAs significantly increased in rice plants after treatment with salt or M. oryzae. The salt-treated plants exhibited enhanced resistance to rice blast disease. RNA sequencing data indicate that S-adenosylmethionine decarboxylase (SAMDC), a key enzyme involved in the synthesis of polyamines, plays a significant role in enhancing plant resistance. Overexpression of rice SAMDC (OsSAMDC) led to a significant decrease of pathogen infection in the transgenic rice plants. Additionally, OsSAMDC overexpression plants accumulated polyamines in the cytosol and apoplast, particularly SPD and SPM. Conversely, the disease resistance and accumulation of PAs were reduced in OsSAMDC-silenced plants. Exogenous application of PAs inhibited the mycelium growth, spore germination, germ tube elongation, and appressorium formation in M. oryzae. These results demonstrated that OsSAMDC-mediated polyamine biosynthesis, especially SPD and SPM, plays an essential role in rice plants to resist biotic and abiotic stresses.

Abstract Background The repair of articular cartilage defects is always a significant clinical challenge in joint treatment. Therefore, the aim of this study was to investigate that the ColII-HA-CS-HAP scaffolds with BMSCs could repair cartilage defects of knee. Methods Bone marrow mesenchymal stem cells (BMSCs) were extracted from rabbits, identified using immunofluorescence staining, and successfully induced into chondrocytes. Type II collagen (ColII) was isolated from bovine cartilage and constructed into scaffolds with hyaluronic acid, chondroitin sulfate, and hydroxyapatite. Then BMSCs were seeded on the ColII-HA-CS-HAP scaffold to detect biocompatibility. Results The results of DAPI fluorescence staining showed that the number of BMSCs on the ColII-HA-CS-HAP scaffolds increased rapidly after culturing for 12 d. The rabbit knee cartilage defect model with a diameter of approximately 3 mm and a thickness of approximately 4 mm was selected to evaluate the regenerative potential of the scaffolds using histological and immunohistochemical analyses. At 6 months, the regenerated cartilage in the ColII-HA-CS-HAP scaffolds with BMSCs was more similar to that of native cartilage than the ColII-HA-CS-HAP scaffold group. Conclusions Our study proved that the ColII-HA-CS-HAP scaffolds with differentiated BMSCs can produce an excellent healing response and repair cartilage defects successfully in a rabbit model.

Abstract Segmentation of brain tissue from MR images provides detailed quantitative brain analysis for accurate diagnosis, detection, and classification of brain diseases, and plays an important role in neuroimaging research and clinical environments. Recently, a plethora of deep learning-based approaches have been employed to achieve brain tissue segmentation in fetuses, infants, and adults with impressive outcomes. However, owing to the existence of noise, motion artifacts, and edge blurriness in MR images, automatically segmenting brain tissue accurately from MR images is still a very challenging task. This survey examines both deep learning and MRI, providing an overview of the latest advances in fetal, infant, and adult brain tissue segmentation techniques based on deep learning. It includes the performance and quantitative analysis of the state-of-the-art methods. Over 100 scientific papers covering various technical aspects, including network architecture, prior knowledge, and attention mechanisms, were reviewed and analyzed. This article also comprehensively discusses these technologies and their potential applications in the future. Brain tissue segmentation provides detailed quantitative brain analysis for accurate diagnosis, detection, and classification of brain diseases, and plays an important role in neuroimaging research and clinical environments.

Due to overactive inflammation and hindered angiogenesis, self-healing of diabetic wounds (DW) remains challenging in the clinic. Platelet-derived exosomes (PLT-Exos), a novel exosome capable of anti-inflammation and pro-angiogenesis, show great potential in DW treatment. However, previous administration of exosomes into skin wounds is topical daub or intradermal injection, which cannot intradermally deliver PLT-Exos into the dermis layer, thus impeding its long-term efficacy in anti-inflammation and pro-angiogenesis. Herein, a dissolvable microneedle-based wound dressing (PLT-Exos@ADMMA-MN) was developed for transdermal and long-term delivery of PLT-Exos. Firstly, a photo-crosslinking methacrylated acellular dermal matrix-based hydrogel (ADMMA-GEL), showing physiochemical tailorability, fast-gelling performance, excellent biocompatibility, and pro-angiogenic capacities, was synthesized as a base material of our dressing. For endowing the dressing with anti-inflammation and pro-angiogenesis, PLT-Exos were encapsulated into ADMMA-GEL with a minimum effective concentration determined by our in-vitro experiments. Then, in-vitro results show that this dressing exhibits excellent properties in anti-inflammation and pro-angiogenesis. Lastly, in-vivo experiments showed that this dressing could continuously and transdermally deliver PLT-Exos into skin wounds to switch local macrophage into M2 phenotype while stimulating neovascularization, thus proving a low-inflammatory and pro-angiogenic microenvironment for DW healing. Collectively, this study provides a novel wound dressing capable of suppressing inflammation and stimulating vascularization for DW treatment.

Abstract Previous research has established that the formation of Gardnerella vaginalis (GV) biofilm is one of the primary reasons for bacterial vaginosis (BV) recurrence. This study was the first to explore the impact of Streptococcus agalactiae (group B Streptococcus, GBS) on GV biofilm in a co-culture scenario. The results revealed that GBS could significantly increased the GV biomass in 48-hours dual-species biofilms. The luxS gene of GBS was significantly higher in dual-species biofilm, while knockdown of the luxS gene resulted in a significant decrease in mono- and dual-species biofilms. Meanwhile, in vitro addition of AI-2 (product of luxS gene) substantially increased biofilm biomass. Furthermore, we found that the expression of two genes related to biofilm formation was notably elevated in GV after receiving AI-2 signals. Collectively, these findings suggest that GBS enhances GV biofilm formation via luxS/AI-2 in an in vitro co-culture model, which in turn may promotes recurrence of BV.

Abstract The key object tracking in sports video scenarios poses a pivotal challenge in the analysis of sports techniques and tactics. In table tennis, due to the small size and rapid motion of the ball, identifying and tracking the table tennis ball through video is a particularly arduous task, where the majority of existing detection and tracking algorithms struggle to meet the practical application requirements in real-world scenarios. To address this issue, this paper proposes a combined technical approach integrating detection and discrimination, tailored to the unique motion characteristics of table tennis. For the detector, we utilize and refine a common video differential detector. As for the discriminator, we introduce GMP (a Graph Max-message Pass Neural Network), which is designed specifically for tracking table tennis balls or similar objects. Furthermore, we enhance an existing dataset for table tennis tracking problems by enriching its scenarios. The results demonstrate that our proposed technical solution performs impressively on both the dataset and the intended real-world environments, showcasing the good scalability of our algorithms and models as well as their potential for application in other scenarios.

Abstract Background Effective screening for colorectal cancer (CRC) enables earlier diagnosis and intervention to improve patient survival. Methods In this study, we prospectively conducted a blood-based CRC screening program for community residents in Hanjiang District, Yangzhou City, and evaluated the screening efficacy of a blood-based multi-locus DNA methylation assay (ColonAiQ). The ColonAiQ-positive rate and colonoscopy participation rate of the population, detection rate of intestinal lesions, and positive predictive value (PPV) of CRC and advanced adenoma (AA) were calculated, and the associated factors were explored. Results A total of 105,285 participants were enrolled from January 2021 to December 2022, all of whom completed the ColonAiQ assay, yielding a positive rate of 6.42% (6759/105,285). The colonoscopy compliance rate was 48.56% (3282/6759). Intestinal lesions were detected in 1773 individuals (54.02%), including 63 cases of CRCs (predominately early-stage), 1195 adenomas (441 cases of AAs), 327 polyps, and 188 other benign lesions. CRC patients exhibited higher ColonAiQ scores and more positive loci compared to healthy individuals. The PPVs were 1.92% for CRC and 13.44% for AA. Among participants, 66,121 (62.8%) completed questionnaires graded by the Asia–Pacific Colorectal Screening score, with 12,139 (18.36%) classified in the high-risk tier. High-risk participants had a higher ColonAiQ-positive rate (11.07%) and PPVs for CRC (3.46%) and AA (22.18%). Factors associated with increased detection rates for CRC and AA included male gender, older age, a history of alcohol consumption, and prior polyps. Conclusions Our study demonstrated that ColonAiQ assay effectively identifies high-risk population. These findings strongly suggest that the ColonAiQ assay represents a promising strategy for the early detection of CRC and AA in individuals at average risk. Trial registration Registered at ClinicalTrials.gov (NCT05336539).

Abstract Flagella propel pathogens through their environments, yet are expensive to synthesize and are immunogenic. Thus, complex hierarchical regulatory networks control flagellar gene expression. Spirochetes are highly motile bacteria, but peculiarly, the archetypal flagellar regulator σ28 is absent in the Lyme spirochete Borrelia burgdorferi. Here, we show that gene bb0268 (flgV) in B. burgdorferi, previously and incorrectly annotated to encode the RNA-binding protein Hfq, is instead a structural flagellar component that modulates flagellar assembly. The flgV gene is broadly conserved in the flagellar superoperon alongside σ28 in many Spirochaetae, Firmicutes and other phyla, with distant homologs in Epsilonproteobacteria. We find that B. burgdorferi FlgV is localized within flagellar basal bodies, and strains lacking flgV produce fewer and shorter flagellar filaments and are defective in cell division and motility. During the enzootic cycle, flgV-deficient B. burgdorferi survive and replicate in Ixodes ticks but are attenuated for infection and dissemination in mice. Our work defines infection timepoints when spirochete motility is most crucial and implicates FlgV as a broadly distributed structural flagellar component that modulates flagellar assembly.

Abstract Pepper diseases and pests typically exhibit small target proportions, diverse shapes and sizes, complex imaging backgrounds, and similarities with the background. Existing detection methods perform poorly in identifying targets of different sizes and shapes within the same scene, and they lack adequate noise suppression capabilities. To address the practical needs of detecting pepper diseases and pests in complex scenarios, we have constructed the first multimodal pepper diseases and pests object detection dataset (PDD). This dataset includes a wide variety of diseases and pests images, along with detailed natural language descriptions of their attributes. Locating the described targets in complex scenes with similar disease symptoms and leaf occlusion presents a significant challenge. To tackle this issue, we propose the PepperNet model for object detection in pepper diseases and pests images using natural language descriptions. This model decomposes complex multimodal features of language and images into explicit attribute features and employs fine-grained multimodal attribute contrast learning strategies. This approach effectively distinguishes subtle local differences between similar objects, achieving fine-grained mapping from language to vision in complex scenarios. Our detection results show a mAP@0.5 of 91.93% and a detection speed of 121.8 frames per second. Visualizations indicate that the model maintains high robustness under varying noise levels and occlusion conditions, demonstrating superior performance and stability across diverse complex scenarios.

Abstract Background Renal cell carcinoma (RCC) is one of the most diagnosed urological malignancies with high mortality and increasing incidence. What’s more, the sunitinib resistance undoubtedly increased the difficulties in RCC therapy. Circular RNAs (circRNAs) are a newly found type of non-coding RNAs with a special circular structure, and are found to participate in the occurrence development, chemoresistance, and prognosis of cancers. Ferroptosis regulates disease progression mainly via polyunsaturated fatty acid metabolism and glutamine catabolic pathways. The mechanism of circRNAs contributed to sunitinib resistance through ferroptosis has not been elucidated clearly. Materials and methods In our research, we identified a novel circRNA Hsa_circ_0072732 from circRNA datasets (GSE108735 and GSE100186). RNase R and Actinomycin D assays were used to detect the loop structure and stability of circRNAs. qRT-PCR and western blot were used for the detection of RNA and protein levels. CCK8 assays were used to detect proliferation and cell viability. Lipid peroxidation (MDA), and reactive oxygen species (ROS) were detected by indicted kits. Dual-luciferase reporter and RNA pull-down assays were used to detect the RNA interactions. Results Our results showed that Hsa_circ_0072732 was highly expressed in RCC cells. Further investigations showed that the silence of Hsa_circ_0072732 could increase RCC sensitivity to sunitinib. Hsa_circ_0072732 contributed to sunitinib chemoresistance by impairing ferroptosis. Hsa_circ_0072732 exerts its function mainly by acting as sponges for miR-548b-3p and regulating the expression SLC7A11. Our research suggests that ferroptosis is involved in sunitinib resistance, and targeting ferroptosis is a promising way for RCC treatment. Conclusion Our research suggests Hsa_circ_0072732 enhanced renal cell carcinoma sunitinib resistance by inhibiting ferroptosis through miR-548b-3p/SLC7A11.

Abstract Background Combination therapy is required for the treatment of moderate acne vulgaris. However, patient compliance in applying multiple topical formulations is poor. Objective To assess the efficacy and safety of a fixed-dose combination gel with adapalene 0.1% and clindamycin 1% (adapalene-clindamycin) relative to adapalene 0.1% monotherapy and clindamycin 1% monotherapy in patients with moderate facial acne vulgaris. Methods This was a randomized, controlled, assessor-blind, phase III study conducted in patients with moderate facial acne vulgaris. Results A total of 1617 patients were enrolled. At week 12, patients in the adapalene–clindamycin gel treatment group showed a significant reduction in the percentage change from baseline in total lesion count (− 66.85%), compared with adapalene alone (− 50.82%) or clindamycin gel alone (− 57.61%). The difference in the least square means of the adapalene–clindamycin gel group and adapalene group, or clindamycin gel group was − 16.08% (95% CI − 19.95% to − 12.21%) and − 9.38% (95% CI − 13.25% to − 5.51%;), respectively. At week 12, 19.28% of participants who received adapalene–clindamycin gel achieved at least 2-grade improvement in IGA, versus 7.74% with adapalene gel (OR 3.05, 95% CI 1.93, 4.80) and 14.77% with clindamycin gel (OR 1.42, 95% CI 0.97, 2.07). The study also achieved all its secondary endpoints. Adverse event rates were mostly mild to moderate and comparable across the three treatment groups. Conclusion Adapalene 0.1%–clindamycin 1% combination gel is well tolerated and demonstrated superior efficacy over 0.1% adapalene gel monotherapy and 1% clindamycin gel monotherapy for the treatment of moderate acne vulgaris. Trial Registration ClinicalTrials.gov identifier NCT03615768.

Abstract Background Conventional management (CM), substantial fertilization and flooding irrigation, has led to soil acidification, the decrease in soil bacterial diversity in bamboo forests. Integration of water and fertilizer management (IWF) can effectively improve the efficiency of water and fertilizer use, but its effect on soil environment, especially on microbial community, is still unclear. Methods Here, we used next-generation high-throughput sequencing to compare soil properties and bacterial communities through different fertilization and irrigation methods under IWF and CM. Results Compared to the control group, CM significantly reduced soil pH and bacterial diversity, while IWF improved soil nutrition status, increased soil bacterial diversity and soil pH to a level similar to the control group. Compared with CM, IWF also improved the relative abundance of beneficial bacteria and copiotrophic bacteria community in the soil, and the bacterial community in IWF was similar to CK. The structure of the bacterial community was also significantly correlated with soil organic matter, total nitrogen, hydrolyzable nitrogen, and available potassium, while soil bacterial diversity was mainly associated with soil hydrolyzable nitrogen. Conclusions IWF can play an important role in preventing soil acidification, the loss of soil bacterial diversity, and improving the structure of the bacterial community under specific conditions.

Abstract Allergic rhinitis (AR) resulted in impairing human health and quality of life seriously. There is currently no definitive remedy for AR. Recent studies have shown that autophagy may regulate airway inflammation. Our comprehension of autophagy and its molecular mechanism in the field of AR condition remains incomplete. Our research endeavors to bridge this knowledge deficit by investigating the correlation between AR and autophagy. The AR-related gene expression profile GSE50223 was screened and downloaded. The “limma” package of R software was utilized to identify differentially expressed genes associated with autophagy. GO, KEGG, and Gene set enrichment analyses were conducted. A PPI network of differentially expressed autophagy-related genes were established and further identified through the CytoHubba algorithm. A receiver operating characteristic curve analysis was employed to evaluate the diagnostic effectiveness of the hub genes and to examine the relationship between autophagy-related genes and AR. Finally, qRT-PCR was carried out to confirm the chosen autophagy-related genes using clinical samples. 21 autophagy-related genes in allergic rhinitis were identified. BECN1, PIK3C3, GABARAPL2, ULK2, and UVRAG were considered as significant differentially expressed autophagy-related genes. However, additional molecular biological experiments will be necessary to elucidate the underlying mechanism connecting autophagy and AR.

Abstract The pathogenesis of pulmonary arterial hypertension (PAH) is closely linked to the abnormal proliferation of pulmonary artery smooth muscle cells. Studies have demonstrated that microRNAs play pivotal roles in the progression of pulmonary hypertension. We found that microRNA-637 (miR-637) and microRNA-661 (miR-661) are expressed at low levels in the serum of PAH patients. Moreover, the overexpression of miR-637 or miR-661 inhibited human pulmonary artery smooth muscle cell (HPASMC) proliferation and migration in hypoxic culture. Mechanistically, we overexpressed these two microRNAs in HPASMCs, and the RNA-sequencing (RNA-seq) results demonstrated that TRIM29 mRNA was suppressed, indicating that TRIM29 is a substrate. TRIM29 accumulates in the serum of patients with PAH and promotes cell proliferation and migration by activating AKT/mTOR signalling. In addition, overexpression of miR-637 or miR-661 reversed TRIM29-mediated HPASMC proliferation and migration. This study revealed that miR-637 and miR-661 are able to inhibit the proliferation ability of HPASMCs under hypoxic conditions through targeting TRIM29, suggesting that the microRNA-637/661/TRIM29 axis may act as a target for PAH treatment.

Abstract Parkinsonian tremor (PT) and Essential tremor (ET) exist as upper limb tremors in clinical practice. Notably, their types of trembling share similar presentations and overlapping frequencies. To enhance objectivity and efficiency in the diagnosis of these two diseases, there is a pressing need for more objective tremor classification procedures. This study proposes a novel multimodal fusion network based on a cross-attention mechanism (MFCA-Net) to automate the classification of upper limb tremors between PTs and ETs. To this end, 140 patients with PTs and ETs were recruited, and acceleration and surface electromyography (sEMG) signals were collected from the forearm during tremor episodes. To comprehensively capture the global and local features of input signals, a multiscale convolution in MFCA-Net was designed. Furthermore, the cross-attention mechanism was applied to fuse the features of the two input signals. The results demonstrate that the final classification accuracy exceeded 97.18% when MFCA-Net was used. Compared with the single acceleration signal and single sEMG signal inputs, the recognition accuracies increased by 18.91% and 10.04%, respectively. Therefore, the proposed MFCA-Net in this study serves as an objective and potential tool for assisting clinicians in the diagnosis of PT and ET patients.

Abstract The rapid development of drone technology has made drones one of the essential tools for acquiring aerial information. The detection and localization of text information through drones greatly enhance their understanding of the environment, enabling tasks of significant importance such as community commercial planning and autonomous navigation in intelligent environments. However, the unique perspective and complex environment during drone photography lead to various challenges in text detection, including diverse text shapes, large-scale variations, and background interference, making traditional methods inadequate. To address this issue, we propose a drone-based text detection method based on boundary adaptation. We first conduct an in-depth analysis of text characteristics from a drone’s perspective. Using ResNet50 as the backbone network, we introduce the proposed Hybrid Text Attention Mechanism into the backbone network to enhance the perception of text regions in the feature extraction module. Additionally, we propose a Spatial Feature Fusion Module to adaptively fuse text features of different scales, thereby enhancing the model’s adaptability. Furthermore, we introduce a text detail transformer by incorporating a local feature extractor into the transformer of the text detail boundary iteration optimization module. This enables the precise optimization and localization of text boundaries by reducing the interference of complex backgrounds, eliminating the need for complex post-processing. Extensive experiments on challenging text detection datasets and drone-based text detection datasets validate the high robustness and state-of-the-art performance of our proposed method, laying a solid foundation for practical applications.

Abstract Superalloys are indispensable materials for the fabrication of high-temperature components in aircraft engines. The discovery of a novel class of γ/γ′ Co-Al-W alloys has ignited a surge of interest in Co-based superalloys, with the aspiration to transcend the inherent constraints of their Ni-based counterparts. However, the conventional methodologies utilized in the design and advancement of new γ/γ′ Co-based superalloys are frequently characterized by their laborious and resource-intensive nature. In this study, we employed a coupled Density Functional Theory (DFT) and machine learning (ML) approach to predict and analyze the stability of the crucial γ′ phase, which is instrumental in expediting the discovery of γ/γ′ Co-based alloys. A dataset comprised of thousands of reliable formation (H f) and decomposition (H d) energies was obtained through high-throughput DFT calculations. Through regression model selection and feature engineering, our trained Random Forest (RF) model achieved prediction accuracies of 98.07% for H f and 97.05% for H d. Utilizing the well-trained RF model, we predicted the energies of over 150,000 ternary and quaternary γ′ phases within the Co-Ni-Fe-Cr-Al-W-Ti-Ta-V-Mo-Nb system. The energy analyses revealed that the presence of Ni, Nb, Ta, Ti, and V significantly reduced the H f and the H d of γ′, while Mo and W deteriorate the stability by increasing both energy values. Interestingly, although Al reduces the H f, it increases H d, thereby adversely affecting the stability of γ′. Applying domain-specific screening based on our knowledge, we identified 1049 out of >150,000 compositions likely to form stable γ′ phases, predominantly distributed across 11 Al-containing systems and 25 Al-free systems. Combining the analysis of CALPHAD method, we experimentally synthesized two new Co-based alloys with γ/γ′ dual-phase microstructures, corroborating the reliability of our theoretical prediction model.

Abstract Objective Lymph node metastasis (LNM) is one of the most common pathways of metastasis in non-small cell lung cancer (NSCLC). Preoperative assessment of occult lymph node metastasis (OLNM) in NSCLC patients is beneficial for selecting appropriate treatment plans and improving patient prognosis. Method A total of 370 NSCLC patients were included in the study. Univariate and multivariate logistic regression analysis were used to screen potential risk factors for OLNM in preoperative NSCLC patients. And establish a nomogram for OLNM in NSCLC patients before surgery. Receiver operating characteristic (ROC) curve, calibration curve, and decision curve analysis (DCA) were used to evaluate the established nomogram. Result Both univariate and multivariate logistic regression analyses suggested that multiple tumors, ERBB2 missense mutation, CA125 levels, CA153 levels, tumor site, tumor length, and serum ferritin are potential risk factors for OLNM in NSCLC patients. The constructed nomogram was evaluated, and the consistency index (C-index) and area under the ROC curve of the model were both 0.846. The calibration curve showed that the predicted values of the model had a high degree of fit with the actual observed values, and DCA suggested that the above indicators had good utility. Conclusion The personalized scoring prediction model constructed based on multiple tumors, ERBB2 miss mutation, CA125 levels, CA153 levels, tumor site, tumor length, and serum ferritin can screen NSCLC patients who may have OLNM.

Abstract Patients with diabetes are susceptible to acute kidney injury (AKI) as compared to counterparts without diabetes. However, data on the long-term clinical outcome of AKI specifically in people with diabetes are still scarce. We sought to study risk factors for and adverse cardio-renal outcomes of AKI in multi-ethnic Southeast Asian people with type 2 diabetes. 1684 participants with type 2 diabetes from a regional hospital were followed an average of 4.2 (SD 2.0) years. Risks for end stage kidney disease (ESKD), major adverse cardiovascular events (MACE) and all-cause death after AKI were assessed by survival analyses. 219 participants experienced at least one AKI episode. Age, cardiovascular disease history, minor ethnicity, diuretics usage, HbA1c, baseline eGFR and albuminuria independently predicted risk for AKI with good discrimination. Compared to those without AKI, participants with any AKI episode had a significantly high risk for ESKD, MACE and all-cause death after adjustment for multiple risk factors including baseline eGFR and albuminuria. Even AKI defined by a mild serum creatinine elevation (0.3 mg/dL) was independently associated with a significantly high risk for premature death. Therefore, individuals with diabetes and any episode of AKI deserve intensive surveillance for cardio-renal dysfunction.

Abstract Background Postoperative radiotherapy (PORT) is crucial for patients with thoracic locally advanced esophageal squamous cell carcinoma (LA-ESCC, pT3-4aN0-3M0) following esophagectomy. However, the appropriate radiation volume has not been well established. This study aimed to determine the optimal PORT volume for LA-ESCC patients. Methods LA-ESCC patients post-esophagectomy were randomly assigned to either the large-field irradiation (LFI, primary lesion and lymph node tumor bed plus elective nodal irradiation) group or the small-field irradiation (SFI, primary lesion and lymph node tumor bed alone) group. Stratification was based on T stage and the number of lymph node metastases. The primary endpoint was disease-free survival (DFS), while the secondary endpoints included overall survival (OS), adverse events, and patterns of initial failure. Results A total of 401 patients were randomly assigned to the intention-to-treat analysis(LFI group, n = 210; SFI group, n = 191). The median DFS of patients in the LFI group was 47.9 months and 48.1 months in the SFI group (HR = 0.87, 95%CI, 0.65 to 1.16; p = 0.32). The estimated one-year and three-year OS rates were 89.2% and 63.2% for patients in the LFI group, compared to 86.6% and 60.7% for the SFI group, respectively. The difference of OS between the two groups was not significant (HR = 0.86, 95%CI, 0.63 to 1.16; p = 0.35). Fewer patients in the LFI group experienced locoregional recurrence compared to the SFI group (12.9% vs 20.4%, p = 0.013). Additionally, locoregional recurrence-free survival of the LFI group was significantly longer than that of SFI group (HR = 0.54, 95%CI, 0.34–0.87; p = 0.01). The most common toxicity was grade 2 esophagitis, observed in 22.9% of the LFI group and 16.8% of the SFI group. Grade 3 adverse events occurred in 6.7% of the LFI group and 2.6% of the SFI group. No grade 4 or 5 toxicities were observed. Adverse events did not significantly differ between the two groups. Conclusions Postoperative radiotherapy, with the specified radiation volume shows encouraging survival outcomes that are comparable to those of neoadjuvant chemoradiotherapy in patients with thoracic LA-ESCC. Both postoperative irradiation fields were found to be feasible and safe.

Abstract RNA methylation is an important regulatory process to determine immune cell function but how it affects the anti-tumor activity of CD8 T cells is not fully understood. Here we show that the N 6-methyladenosine (m6A) RNA reader YTHDF2 is highly expressed in early effector or effector-like CD8 T cells. We find that YTHDF2 facilitates nascent RNA synthesis, and m6A recognition is fundamental for this distinctively nuclear function of the protein, which also reinforces its autoregulation at the RNA level. Loss of YTHDF2 in T cells exacerbates tumor progression and confers unresponsiveness to PD-1 blockade in mice and in humans. In addition to initiating RNA decay that is necessary for mitochondrial fitness, YTHDF2 orchestrates chromatin changes that promote T cell polyfunctionality. YTHDF2 interacts with IKZF1/3, which is important for sustained transcription of their target genes. Accordingly, immunotherapy-induced efficacy could be largely restored in YTHDF2-deficient T cells through combinational use of IKZF1/3 inhibitor lenalidomide in a mouse model. Thus, YTHDF2 coordinates epi-transcriptional and transcriptional networks to potentiate T cell immunity, which could inform therapeutic intervention.

Abstract Berberine (BBR), a widely recognized traditional Chinese medicine, has attracted considerable attention for its promising anti‐inflammatory effects. The activation of nuclear factor erythroid 2‐related factor 2 (Nrf2) effectively safeguards against organ damage stemming from sepsis‐induced oxidative stress and inflammatory responses. This study examined the potential of BBR in alleviating sepsis‐induced acute gastric injury, with a particular focus on elucidating whether its mechanism of action involves the activation of the Nrf2 signaling pathway. Following intraperitoneal injection of BBR, mice were subjected to the cecal ligation and puncture (CLP) method to induce sepsis. In vitro experiments involved pre‐treating the normal gastric epithelial cells (GES‐1) with BBR, followed by treatment with lipopolysaccharide (LPS). Functional assays were then performed to assess cell proliferation and apoptosis. To validate the role of Nrf2 in pyroptosis and inflammation, siRNA targeting Nrf2 (si‐Nrf2) was transfected into LPS‐treated GES‐1 cells. Additionally, mice were administered the Nrf2 inhibitor ML385 to confirm the protective effects of BBR in vivo. BBR displayed a dose‐dependent effect in mitigating gastric tissue damage, suppressing the release of inflammatory cytokines, and reducing the expression of NLRP3, ASC, and GSDMD‐N. In vitro, BBR fostered GES‐1 cell proliferation, hindered apoptosis, and suppressed the levels of TNF‐α, IL‐18, IL‐1β, NLRP3, ASC, and GSDMD‐N. Further analysis revealed that knocking down Nrf2 reversed BBR's inhibitory effect on pyroptosis in LPS‐treated GES‐1 cells. Through binding to Keap1, BBR efficiently prevented the ubiquitination and degradation of Nrf2, ultimately promoting its nuclear translocation. In vivo experiments confirmed that ML385 reversed the protective effect of BBR on pyroptosis and inflammation. Our research reveals that BBR interacts with Keap1 to activate the Keap1/Nrf2 signaling pathway in gastric epithelial cells, thereby suppressing pyroptosis and inflammation in sepsis‐induced acute gastric injury.

Abstract Objective This study aimed to identify risk factors contributing to the early onset of patellofemoral osteoarthritis (PFOA) within the first two years following anterior cruciate ligament reconstruction (ACLR) using a hamstring tendon autograft. Methods Participants aged 18 to 40 who had undergone ACLR within the past two years were included in this study, along with a control group of healthy volunteers. Magnetic resonance imaging (MRI) data were obtained preoperatively, at two years postoperatively, and from the control group. T-tests were used to assess differences in patellofemoral alignment (PA) and trochlear morphology (TM) between the pre- and post-ACLR patients and healthy controls. The incidence of PFOA was recorded, and associations between PA, TM, and clinical parameters were evaluated in patients with and without PFOA. Logistic regression analysis was conducted to identify potential risk factors for PFOA development. Results A total of 177 patients, with a mean follow-up period of 22.17 ± 5.09 months and a mean age of 26.4 ± 5.6 years, were included in the study. Following ACL injury, significant alterations in patellar tilt angle (PTA), tuberositas tibae-trochlear groove distance (TT-TG), Insall-Salvati ratio (ISR), and static anterior tibial translation (SATT) were observed compared to the control group. Postoperatively, deviations in PTA and SATT remained significant when compared to healthy controls. Of the 177 patients, 68 (38.42%) developed early-onset PFOA. Factors associated with the early onset of PFOA included age at the time of surgery, the interval between injury and surgery, PTA, bisect offset (BO), sulcus angle (SA), thigh circumference, SATT, and partial meniscectomy. Conclusion Significant differences in PTA, TT-TG, ISR, and SATT were identified between patients who underwent ACLR and healthy controls. Postoperatively, there was no correction in PTA or SATT, which remained significantly altered. Factors such as age at the time of surgery, PTA, BO, SA, ISR, SATT, thigh circumference, partial meniscectomy, and the time interval between injury and surgery were associated with the early onset of PFOA within two years post-ACLR. These findings may aid in the prevention of PFOA by identifying individuals at higher risk for early development.

This study aimed to research the feasibility of incorporating 100% municipal solid waste incineration bottom ash (MSWIBA) as a replacement for fine aggregates in engineered cementitious composites (ECCs). To improve mechanical properties, three types of polymer fibers (PVA, PP, and PE) were used with different dosages of 0–2% by volume. The effect of fibers content on compressive strength, elastic modulus, and other performance indicators such as peak strain, ultimate strain, damage evolution, and toughness index was studied. Results showed that while the elastic modulus and peak stress slightly decreased with increase of fiber content due to fiber agglomeration and increased macro-porosity, fibers significantly improved the deformation capacity and toughness. For instance, the MSWIBA-ECCs with 2% PP fibers showed the highest compressive damage energy of 205.47 J, a 79.48% increase over the control group, showing superior toughness. Additionally, this study developed a new compressive constitutive model that accurately predicted compressive stress-strain behavior considering fiber characteristics. Environmental assessment showed that MSWIBA-ECCs effectively immobilized heavy metals (Cu, Ni, Pb, Zn), with a solidification efficiency of 97%, ensuring compliance with Chinese environmental requirements. These findings suggest that MSWIBA-ECCs, combined with optimized fiber content, offer a sustainable and high-performance alternative for construction applications.

The commercially available drug-eluting stent with limus (rapamycin, everolimus, etc.) or paclitaxel inhibits smooth muscle cell (SMC), reducing the in-stent restenosis, whereas damages endothelial cell (EC) and delays stent reendothelialization, increasing the risk of stent thrombosis (ST) and sudden cardiac death. Here we present a new strategy for promoting stent reendothelialization and preventing ST by exploring the application of precise molecular targets with EC specificity. Proteomics was used to investigate the molecular mechanism of EC injury caused by rapamycin. Endothelial protein C receptor (EPCR) was screened out as a crucial EC-specific effector. Limus and paclitaxel repressed the EPCR expression, while overexpression of EPCR protected EC from coating (eluting) drug-induced injury. Furthermore, the ligand activated protein C (APC), polypeptide TR47, and compound parmodulin 2, which activated the target EPCR, promoted EC functions and inhibited platelet or neutrophil adhesion, and enhanced rapamycin stent reendothelialization in the simulated stent environment and in vitro. In vivo, the APC/rapamycin-coating promoted reendothelialization rapidly and prevented ST more effectively than rapamycin-coating alone, in both traditional metal stents and biodegradable stents. Additionally, overexpression or activation of the target EPCR did not affect the cellular behavior of SMC or the inhibitory effect of rapamycin on SMC. In conclusion, EPCR is a promising therapeutical agonistic target for pro-reendothelialization and anti-thrombosis of eluting stent. Activation of EPCR protects against coating drugs-induced EC injury, inflammatory cell, or platelet adhesion onto the stent. The novel application formula for APC/rapamycin-combined eluting promotes stent reendothelialization and prevents ST.

ObjectivesAs wheel loading on the vehicle decks of ro-ro ships may introduce difficulties for structural analysis due to the uncertainty of their quantities, ranges, and positions, it is necessary to study the equivalence and simplification of such loads. MethodsUsing a multi-span beam model as an idealized vehicle deck secondary member, wheel loading is simulated by distributed load and concentrated force respectively, and several structural responses are compared and analyzed. Furthermore, an analysis is made of the change in structural response after multiple wheel loadings have been simultaneously transformed into concentrated force. ResultsThe calculation results suggest that for vehicle decks with an ordinary arrangement, such equivalence and simplification tends to be safer and will not bring significant changes to the structural response. ConclusionsBased on the above conclusions, a reasonable equivalent multi-wheel loading method is provided for engineering application, thus contributing to the design simplification and strength verification of vehicle decks.

Abstract Objectives This study investigates curcumin's neuroprotective role and its potential in promoting neurogenesis in progenitor cells within the brain. Notably, curcumin's antioxidant properties have been implicated in Alzheimer's disease treatment. However, the association between curcumin's antioxidative effects and its impact on neural stem cells (NSCs) remains to be elucidated. Methods C17.2 neural stem cells were utilized as a model to simulate oxidative stress, induced by hydrogen peroxide (H2O2). We quantified the levels of superoxide dismutase (SOD), malondialdehyde (MDA), and intracellular reactive oxygen species (ROS), alongside the gene expression of SOD1 and SOD2, to assess intracellular oxidative stress. Additionally, Western blot analysis was conducted to measure the expressions of LC3‐II, Beclin‐1, and phosphorylated ERK (p‐ERK), thereby evaluating autophagy and ERK signaling pathway activation. Results Treatment with curcumin resulted in a reduction of MDA and ROS levels, suggesting a protective effect on NSCs against oxidative damage induced by H2O2. Furthermore, a decrease in the relative expressions of LC3‐II, Beclin‐1, and p‐ERK was observed post‐curcumin treatment. Conclusions The findings suggest that curcumin may confer protection against oxidative stress by attenuating autophagy and deactivating the ERK1/2 signaling pathways, which could contribute to therapeutic strategies for Alzheimer's disease.

Abstract Esophageal squamous cell carcinoma (ESCC) is a prevalent malignancy within the digestive system, characterized by high incidence and mortality rates. The biological role of REEP5 in ESCC progression remains poorly understood, despite its associations with various diseases, potentially accelerating tumor malignancy. We retrieved RNA-seq data and clinical information from 179 ESCC patients from the Gene Expression Omnibus (GEO) and 93 patients from The Cancer Genome Atlas (TCGA) databases. Bioinformatics analyses were conducted to explore the biological functions of REEP5 in ESCC, its role in the tumor microenvironment, and its prognostic value. Additionally, utilizing single-cell RNA-seq (scRNA-seq) data from 3 ESCC patients in the GEO database, we performed cluster analyses to investigate cell-specific expression differences of REEP5 between cancerous and adjacent non-cancerous tissues. Molecular biology experiments were also conducted to validate REEP5 expression disparities between tumor and non-tumor tissues. Compared to normal tissues, REEP5 was significantly enriched in ESCC tissues. High REEP5 expression was closely associated with poor prognosis in ESCC patients. Gene Ontology (GO) analysis revealed strong correlations between REEP5 and processes such as mRNA splicing and protein stabilization. Gene Set Enrichment Analysis (GSEA) and Gene Set Variation Analysis (GSVA) indicated positive correlations between REEP5 and mRNA spliceosome assembly and disassembly. Pearson correlation analysis demonstrated positive associations between REEP5 and cancer-inhibitory immune checkpoints CTLA-4, TIM-3, and HVEM. Single-cell clustering and CIBERSORT analysis showed that REEP5 expression was closely related to T-cell infiltration in ESCC, with significant enrichment effects observed in CD8+ T-cell infiltration. REEP5 expression is closely correlated with the pathological and molecular pathology of ESCC, potentially playing a crucial role in Mast cell or T-cell-mediated immune responses in ESCC. Therefore, REEP5 holds promise as a novel therapeutic target for ESCC.

Abstract Type IV pili (T4P) produced by the pathogen Pseudomonas aeruginosa play a pivotal role in adhesion, surface motility, biofilm formation, and infection in humans. Despite the significance of T4P as a potential therapeutic target, key details of their dynamic assembly and underlying molecular mechanisms of pilus extension and retraction remain elusive, primarily due to challenges in isolating intact T4P machines from the bacterial cell envelope. Here, we combine cryo-electron tomography with subtomogram averaging and integrative modelling to resolve in-situ architectural details of the dynamic T4P machine in P. aeruginosa cells. The T4P machine forms 7-fold symmetric cage-like structures anchored in the cell envelope, providing a molecular framework for the rapid exchange of major pilin subunits during pilus extension and retraction. Our data suggest that the T4P adhesin PilY1 forms a champagne-cork-shaped structure, effectively blocking the secretin channel in the outer membrane whereas the minor-pilin complex in the periplasm appears to contact PilY1 via the central pore of the secretin gate. These findings point to a hypothetical model where the interplay between the secretin protein PilQ and the PilY1-minor-pilin priming complex is important for optimizing conformations of the T4P machine in P. aeruginosa, suggesting a gate-keeping mechanism that regulates pilus dynamics.

Abstract Background High-temperature fermentation technology is promising in improving fermentation speed and product quality, and thereby widely used in various fields such as food, pharmaceuticals, and biofuels. However, extreme temperature conditions can disrupt cell membrane structures and interfere with the functionality of biological macromolecules (e.g. proteins and RNA), exerting detrimental effects on cellular viability and fermentation capability. Results Herein, a microbial thermotolerance improvement strategy was developed based on adaptive laboratory evolution (ALE) for efficient high-temperature fermentation. Employing this strategy, we have successfully obtained Corynebacterium glutamicum strains with superior resistance to high temperatures. Specifically, the genome analysis indicated that the evolved strains harbored 13 missense genetic mutations and 3 same-sense genetic mutations compared to the non-evolved parent strain. Besides, reverse transcription quantitative PCR analysis (RT qPCR) of the hrcA-L119P mutant demonstrated that both groEL genes were upregulated under 42 °C, which enabled the construction of robust strains with improved heat tolerance. Furthermore, a significant increase in FAS-IA and FAS-IB expression of the fasR-L102F strain was proved to play a key role in protecting cells against heat stress. Conclusions This work systematically reveals the thermotolerance mechanisms of Corynebacterium glutamicum and opens a new avenue for revolutionizing the design of cell factories to boost fermentation efficiency.

Abstract Epicardial adipose tissue (EAT) significantly contributes to the progression of cardiovascular diseases (CVDs). However, manually quantifying EAT volume is labor-intensive and susceptible to human error. Although there have been some deep learning-based methods for automatic quantification of EAT, they are mostly uninterpretable and fail to harness the complete anatomical characteristics. In this study, we proposed an enhanced deep learning method designed for EAT quantification on coronary computed tomography angiography (CCTA) scan, which integrated both data-driven method and specific morphological information. A total of 108 patients who underwent routine CCTA examinations were included in this study. They were randomly assigned to training set (n = 60), validation set (n = 8), and test set (n = 40). We quantified and calculated the EAT volume based on the CT attenuation values within the predicted pericardium. The automatic method demonstrated strong agreement with expert manual quantification, yielding a median Dice score coefficients (DSC) of 0.916 (Interquartile Range (IQR): 0.846–0.948) for 2D slices. Meanwhile, the median DSC for the 3D volume was 0.896 (IQR: 0.874–0.908) between these two measures, with an excellent correlation of 0.980 (p

Abstract Accurate and timely pest and disease monitoring during the cultivation process of traditional Chinese medicinal materials is crucial for ensuring optimal growth, increased yield, and enhanced content of effective components. This paper focuses on the essential requirements for pest and disease monitoring in a planting base of Cinnamomum Camphora var. Borneol (CCB) and presents a solution using unmanned aerial vehicle (UAV) images to address the limitations of real-time and on-site inspections. In contrast to existing solutions that rely on advanced sensors like multispectral or hyperspectral sensors mounted on UAVs, this paper utilizes visible light sensors directly. It introduces an ensemble learning approach for pest and disease monitoring of CCB trees based on RGB-derived vegetation indices and a combination of various machine learning algorithms. By leveraging the feature extraction capabilities of multiple algorithms such as RF, SVM, KNN, GBDT, XGBoost, GNB, and ELM, and incorporating morphological filtering post-processing and genetic algorithms to assign weights to each classifier for optimal weight combination, a novel ensemble learning strategy is proposed to significantly enhance the accuracy of pest and disease monitoring of CCB trees. Experimental results validate that the proposed method can achieve precise pest and disease monitoring with reduced training samples, exhibiting high generalization ability. It enables large-scale pest and disease monitoring at a low cost and high precision, thereby contributing to improved precision in the cultivation management of traditional Chinese medicinal materials.

Abstract Memories are crucial for daily life, yet the network-level organizing principles governing neural representations of experiences remain unknown. Employing dual-site in vivo recording in freely behaving male mice, here we show that hippocampal dorsal CA1 (dCA1) and basolateral amygdala (BLA) utilize distinct coding strategies for novel experiences. A small assembly of BLA neurons emerged active during memory acquisition and persisted through consolidation, whereas most dCA1 neurons were engaged in both processes. Machine learning decoding revealed that dCA1 population spikes predicted BLA assembly firing rate, suggesting that most dCA1 neurons concurrently index an episodic event by rapidly establishing weighted communication with a specific BLA assembly – a process we term “many-to-one weighted mapping.” We also found that dCA1 reactivations preceded BLA assembly activity preferably during elongated and enlarged dCA1 ripples. Using a closed-loop strategy, we demonstrated that suppressing BLA activity after large dCA1 ripples impaired memory. These findings highlight a many-to-one weighted mapping mechanism underlying both the acquisition and consolidation of new memories.

Abstract Background Accurate and up-to-date estimates of the global cancer burden in adolescents and young adults (AYA) are scarce. This study aims to assess the global burden and trends of AYA cancer, with a focus on socioeconomic disparities, to inform global cancer control strategies. Methods AYA cancer, defined as cancer occurring in individuals aged 15–39, was analyzed using data from the Global Burden of Disease (GBD) 2021 study and the Global Cancer Observatory (GLOBOCAN) 2022 project. We examined the global burden by age, sex, geographic location, and Human Development Index (HDI), as well as its temporal trends. Primary outcomes included age-standardized incidence and mortality rates (ASIR, ASMR) and the average annual percent change (AAPC). Results In 2022, an estimated 1,300,196 incidental cases and 377,621 cancer-related deaths occurred among AYAs worldwide, with an ASIR of 40.3 per 100,000 and an ASMR of 11.8 per 100,000. The most common cancers were breast, thyroid, and cervical, while the leading causes of death were breast, cervical, and leukemia. The incidence and mortality were disproportionately higher among females (ASIR: 52.9 for females vs. 28.3 for males; ASMR: 13.1 for females vs. 10.6 for males). Countries with higher HDI experienced a higher incidence of AYA cancers (ASIR: 32.0 [low HDI] vs. 54.8 [very high HDI]), while countries with lower HDI faced a disproportionately higher mortality burden (ASMR: 17.2 [low HDI] vs. 8.4 [very high HDI]) despite their relatively low incidence. Disproportionality and regression measures highlighted significant HDI-related inequalities. AYA cancer incidence was stable from 2000 to 2011 (AAPC: − 0.04) but increased from 2012 to 2021 (AAPC: 0.53), driven by growing gonadal and colorectal cancers. Mortality decreased substantially from 2000 to 2011 (AAPC: − 1.64), but the decline slowed from 2012 (AAPC: − 0.32) probably due to increased deaths from gonadal cancers. These trends varied by sex, cancer type, geography, and HDI. Conclusion AYA cancers present a significant and growing global burden, with marked disparities across sex, geographic locations, and HDI levels. Policymakers should prioritize equitable resource allocation and implement targeted interventions to reduce these inequalities, particularly in low-HDI regions and with regard to gonadal cancers.

Biosafety hazards can trigger a host immune response after infection, invasion, or contact with the host. Whether infection with a microorganism results in disease or biosafety concerns depends to a large extent on the immune status of the population. Therefore, it is essential to investigate the immunological characteristics of the host and the mechanisms of biological threats and agents to protect the host more effectively. Emerging and re-emerging infectious diseases, such as the current coronavirus disease 2019 (COVID-19) pandemic, have raised concerns regarding both biosafety and immunology worldwide. Interdisciplinary studies involved in biosafety and immunology are relevant in many fields, including the development of vaccines and other immune interventions such as monoclonal antibodies and T-cells, herd immunity (or population-level barrier immunity), immunopathology, and multispecies immunity, i.e., animals and even plants. Meanwhile, advances in immunological science and technology are occurring rapidly, resulting in important research achievements that may contribute to the recognition of emerging biosafety hazards, as well as early warning, prevention, and defense systems. This review provides an overview of the interdisciplinary field of biosafety and immunology. Close collaboration and innovative application of immunology in the field of biosafety is becoming essential for human health.

The separation and recovery of uranium from natural water is of great significance to the exploitation of unconventional uranium resources. In our paper, a novel polyacrylonitrile(PAN)/Hummers oxidized lotus seedpod carbon composite was prepared, and adsorption of U(Ⅵ) ion from U(Ⅵ)-CO3 solution under weakly alkaline condition was also studied. Batch adsorption experimental results show that at room temperature, pH=8.0, ρ(U(Ⅵ))=50 mg/L, cT(CO3)=2 mmol/L, the adsorption reaches equilibrium after 840 min, and the maximum adsorption capacity is about 51.92 mg/g. The increase of the pH values, calcium ion concentration, magnesium ion concentration and carbonate concentration inhibit the U(Ⅵ) adsorption. Thermodynamic results indicate that it is a spontaneous, endothermic chemical adsorption process. Characterization results show that the composite displays good structure stability during U(Ⅵ) adsorption process, meanwhile, the phenolic —OH and —COOH(C=O) are the main adsorption sites on the composite surfaces. In the presence of calcium/magnesium ions, the order of adsorption affinity of U(Ⅵ) on the composite material is as follows: Mg-U(Ⅵ)-CO3 system＞Ca-U(Ⅵ)-CO3 system. The results can provide the new materials for the separation and extraction of uranium from natural uranium-containing water.

In advanced hepatocellular carcinoma (HCC) tissues, M2-like tumor-associated macrophages (TAMs) are in the majority and promotes HCC progression. Contrary to the pro-tumor effect of M2-like TAMs, M1-like TAMs account for a small proportion and have anti-tumor effects. Since TAMs can switch from one type to another, reprogramming TAMs may be an important treatment for HCC therapy. However, the mechanisms of phenotypic switch and reprogramming TAMs are still obscure. In this study, we analyzed differential genes in normal macrophages and TAMs, and found that loss of MANF in TAMs accompanied by high levels of downstream genes negatively regulated by MANF. MANF reprogrammed TAMs into M1 phenotype. Meanwhile, loss of MANF promoted HCC progression in HCC patients and mice HCC model, especially tumor neovascularization. Additionally, macrophages with MANF supplement suppressed HCC progression in mice, suggesting MANF supplement in macrophage was an effective treatment for HCC. Mechanistically, MANF enhanced the HSF1–HSP70-1 interaction, restricted HSF1 in the cytoplasm of macrophages, and decreased both mRNA and protein levels of HSP70-1, which in turn led to reprogramming TAMs, and suppressing neovascularization of HCC. Our study contributes to the exploration the mechanism of TAMs reprogramming, which may provide insights for future therapeutic exploitation of HCC neovascularization.

Abstract Introduction Arterial calcification, an independent predictor of cardiovascular events, increases morbidity and mortality in patients with diabetes mellitus (DM), but its mechanisms remain unclear. Extracellular vesicles (EVs) play an important role in intercellular communication. The study investigates the role and potential mechanisms of EVs derived from endothelial cells (ECs) in regulating vascular smooth muscle cell (VSMC) calcification under high glucose (HG) condition, with a goal of developing effective prevention and treatment strategies for diabetic arterial calcification. Results The results showed that EVs derived from HG induced ECs (ECHG-EVs) exhibited a bilayer structure morphology with a mean diameter of 74.08 ± 31.78 nm, expressing EVs markers including CD9, CD63 and TSG101, but not express calnexin. ECHG-EVs was internalized by VSMCs and induced VSMC calcification by increasing Runx2 expression and mineralized nodule formation. The circ_0008362 was enriched in ECHG-EVs, and it can be transmitted to VSMCs to promote VSMC calcification both in vitro and in vivo. Mechanistically, miR-1251-5p might be one of the targets of circ_0008362 and they were co-localization in the cytoplasm of VSMCs. Runx2 was identified as the downstream target of miR-1251-5p, and circ_0008362 acted as a sponge, enhancing Runx2 expression and then promoted VSMC calcification. Besides, circ_0008362 could directly interact with Runx2 to aggravate VSMC calcification. Notably, DiR-labelled ECHG-EVs was detected in the vessels of mice. Meanwhile, the level of circ_0008362 and Runx2 were increased significantly, while the expression of miR-1251-5p was decreased significantly in calcified artery tissues of mice. However, inhibiting the release of EVs by GW4869 attenuated arterial calcification in diabetic mice. Finally, the level of circulation of plasma EVs circ_0008362 was significantly higher in patients with DM compared with normal controls. Elevated levels of plasma EVs circ_0008362 were associated with more severe coronary and aorta artery calcification in patients with DM. Conclusions Our findings suggested that circ_0008362 was enriched in EVs derived from ECs and promoted VSMC calcification under HG conditions, both by sponging miR-1251-5p to upregulate Runx2 expression and through direct interaction with Runx2. Furthermore, elevated levels of plasma EVs circ_0008362 were associated with more severe coronary and aorta artery calcification in patients with DM. These results may serve as a potential prevention and therapeutic target for diabetic arterial calcification. Graphical abstract

Abstract The health-related quality of life (HRQOL) of college students is not promising and needs to be improved through effective interventions. This study aimed to investigate the associations of nutrition literacy (NL) with HRQOL and anxiety among college students, and to identify the role of anxiety in the relationship between NL and HRQOL. The cross-sectional survey was conducted via the “Wenjuanxing” platform from September to November 2023. The Food and Nutrition Literacy Questionnaire (FNLQ), the Generalized Anxiety Disorder (GAD-7) diagnostic tool and the SF-12 scale were used to assess NL, anxiety, and HRQOL, respectively. Logistic regression models, mediation analysis, additive and multiplicative interaction analyses were used. 2066 college students participated in the analysis. After adjusting for potential confounders, we found that college students with higher NL had higher HRQOL (OR = 2.52, 95% CI: 2.09–3.03, p

Abstract Background Non-small cell lung cancer (NSCLC) presents a significant challenge in the medical field due to its high incidence and resistance to chemotherapy. Chemoresistance in NSCLC diminishes treatment efficacy and contributes to poor patient outcomes. Matrine alkaloids have shown promise in reversing chemotherapy resistance in NSCLC by targeting DNA repair mechanisms. Methods Utilizing molecular dynamics simulations, we explored the interactions between Matrine alkaloids and DNA repair-related proteins to elucidate their impact on NSCLC cells. In vitro experiments involved treating A549/DDP cells with Matrine alkaloids to evaluate their sensitizing effects on lung cancer cells. Additionally, animal model experiments were conducted to validate the therapeutic potential of Matrine alkaloids in NSCLC treatment. Results Our findings demonstrate that Matrine alkaloids disrupt DNA damage repair processes in NSCLC cells, leading to increased sensitivity to chemotherapy. Molecular docking studies revealed the intricate mechanisms by which Matrine alkaloids interact with DNA repair proteins, impacting cell survival and proliferation. Both cell experiments and animal models confirmed the chemosensitizing effects of Matrine alkaloids in NSCLC treatment. Conclusion Matrine alkaloids offer a promising avenue for overcoming chemotherapy resistance in NSCLC by interfering with DNA repair pathways. This study lays a solid foundation for future clinical investigations into the potential of Matrine alkaloids as effective therapeutic agents for enhancing NSCLC treatment outcomes.

Abstract Ground‐based phenological observation data are the most accurate phenological monitoring data currently available. Making effective use of available information on social media to retrieve phenological data is of considerable value in alleviating the lack of phenological data in regions with missing observation sites. In this study, a logistic curve fitting method was developed to extract phenological data on specific species from social media data. After verifying the relationship between the site observation data and the temperature, timing data for two typical phenological phenomena in China, namely cherry blossom flowering in spring and ginkgo leaf coloration in autumn were reconstructed and published. The data availability is from 2010 to 2019 in 176 cities and 2009 to 2018 in 155 cities. This dataset is an effective supplement for existing phenological data, and this method also provides a reference for obtaining phenological data for specific species.

Abstract Background Modified furosemide responsiveness index (mFRI) is a novel biomarker for assessing diuretic response and AKI progression in patients with early AKI. However, the comparative predictive performance of mFRI and novel renal biomarkers for adverse renal outcomes remains unclear. In a single-center prospective study, we aimed to evaluate the discriminatory abilities of mFRI and other novel renal biomarkers in predicting AKI progression and prognosis in patients with initial mild and moderate AKI (KDIGO stage 1 to 2). Results Patients with initial mild and moderate AKI within 48 h following cardiac surgery were included in this study. The mFRI, renal biomarkers (including serum or urinary neutrophil gelatinase-associated lipocalin [sNGAL or uNGAL], serum cystatin C, urinary N-acetyl-beta-D-glycosaminidase [uNAG], urinary albumin-to-creatinine ratio) and cytokines (TNF, IL-1β, IL-2R, IL-6, IL-8, and IL-10) were measured at AKI diagnosis. The mFRI was calculated for each patient, which was defined as 2-hour urine output divided by furosemide dose and body weight. Of 1013 included patients, 154 (15.2%) experienced AKI progression, with 59 (5.8%) progressing to stage 3 and 33 (3.3%) meeting the composite outcome of hospital mortality or receipt of renal replacement therapy (RRT). The mFRI showed non-inferiority or potential superiority to renal biomarkers and cytokines in predicting AKI progression (area under the curve [AUC] 0.80, 95% confidence interval [CI] 0.77–0.82), progression to stage 3 (AUC 0.87, 95% CI 0.85–0.89), and composite outcome of death and receipt of RRT (AUC 0.85, 95% CI 0.82–0.87). Furthermore, the combination of a functional biomarker (mFRI) and a urinary injury biomarker (uNAG or uNGAL) resulted in a significant improvement in the prediction of adverse renal outcomes than either individual biomarker (all P

Abstract Background Plant-specific TIFY proteins play crucial roles in regulating plant growth, development, and various stress responses. However, there is no information available about this family in Artemisia argyi, a well-known traditional medicinal plant with great economic value. Results A total of 34 AaTIFY genes were identified, including 4 TIFY, 22 JAZ, 5 PPD, and 3 ZML genes. Structural, motif scanning, and phylogenetic relationships analysis of these genes revealed that members within the same group or subgroup exhibit similar exon-intron structures and conserved motif compositions. The TIFY genes were unevenly distributed across the 15 chromosomes. Tandem duplication events and segmental duplication events have been identified in the TIFY family in A. argyi. These events have played a crucial role in the gene multiplication and compression of different subfamilies within the TIFY family. Promoter analysis revealed that most AaTIFY genes contain multiple cis-elements associated with stress response, phytohormone signal transduction, and plant growth and development. Expression analysis of roots and leaves using RNA-seq data revealed that certain AaTIFY genes showed tissue-specific expression patterns, and some AaTIFY genes, such as AaTIFY19/29, were found to be involved in regulating salt and saline-alkali stresses. In addition, RT-qPCR analysis showed that TIFY genes, especially AaTIFY19/23/27/29, respond to a variety of hormonal treatments, such as MeJA, ABA, SA, and IAA. This suggested that TIFY genes in A. argyi regulate plant growth and respond to different stresses by following different hormone signaling pathways. Conclusion Taken together, our study conducted a comprehensive identification and analysis of the TIFY gene family in A. argyi. These findings suggested that TIFY might play an important role in plant development and stress responses, which laid a valuable foundation for further understanding the function of TIFY genes in multiple stress responses and phytohormone crosstalk in A. argyi.

Abstract Yoga is effective in binge eating disorder (BED) treatment, but it does not seem effective enough to improve low physical fitness. In contrast, high-intensity interval training (HIIT) is effective in improving physical fitness but has never been studied in the context of BED. In the study, 47 young inactive females with mild to moderate BED were recruited and randomly assigned to a HIIT group (HIIT), a Yoga group (YG), or a control group (CG; age, 19.47 ± 0.74, 19.69 ± 0.874, and 19.44 ± 0.63 years; BMI, 21.07 ± 1.66, 21.95 ± 2.67, and 20.68 ± 2.61 kg/m2, respectively). The intervention groups participated in 8-week specific exercises, while the CG maintained their usual daily activity. Before and after the training, participants were evaluated for BED using the binge eating scale (BES) and for physical fitness. The obtained data were compared within groups and between groups, and a correlation analysis between BES and physical fitness parameters was performed. After the training, the YG presented significant improvements in BES (− 20.25%, p = 0.006, η p 2 = 0.408), fat mass (FM, − 3.13%, p = 0.033, η p 2 = 0.269), and maximal oxygen consumption (VO2max, 11.51%, p = 0.000, η p 2 = 0.601), whereas the HIIT showed significant improvements in body weight (BW, − 1.78%, p = 0.006, η p 2 = 0.433), FM (− 3.94%, p = 0.033, η p 2 = 0.285), and BMI (− 1.80%, p = 0.006, η p 2 = 0.428), but not in BES. Comparisons between groups revealed that both HIIT and YG had significantly higher VO2max levels than CG (HIIT 12.82%, p = 0.006, η p 2 = 0.088; YG: 11.90%, p = 0.009, η p 2 = 0.088) with no difference between HIIT and YG. Additionally, YG presented significantly lower BES than both HIIT (15.45%, p = 0.02, η p 2 = 0.03) and CG (11.91%, p = 0.022, η p 2 = 0.03). In conclusion, Yoga is an effective treatment for BED, but HIIT is not, despite its high efficacy in improving physical fitness.

Abstract Only a few Swiss fossil localities are known globally and of which, the UNESCO World Heritage Site Monte San Giorgio, which extends from Switzerland into Italy, is the most important one. Following the discovery of the occurrence of articulated skeletons of marine reptiles in the local mines, large excavations were organized by Bernhard Peyer from the University of Zurich starting 1924. With this collection of articles, we commemorate the successful excavations and research, which initiated the publication of a series of monographies, mostly on the vertebrates but also on the invertebrates of this locality. Especially with the discovery of several remarkably similar Konservat-Lagerstätten in China, the discoveries from Monte San Giorgio gained global relevance. New methodologies such as computed tomography produced a wealth of new data, particularly on endocranial anatomy of several tetrapods.

The rapid advancement of generative AI technology offers new opportunities for the innovation and transformation of education. However, this also brings forth risks and challenges, including the potential to exacerbate educational inequality and integrity. This study aims to address the extensive controversies surrounding the application of generative AI technology in education by providing an objective and comprehensive understanding of its current state, development in educational contexts. Using the CiteSpace and VOSviewer software, we conducted visual analyses of relevant literature from the Web of Science core collection pertaining to the application of generative AI in education. Subsequently, we identified productive journals, productive articles, collaboration patterns, article hotspots, and prevalent topics in this field. This study will facilitate the promotion of in-depth research and practical implementation of AI in education.

Multi-layer linings have been widely used in deep rheological soft rock tunnels for the excellent performance in preventing large-deformation hazards. Previous studies have focused on the bearing capability of multi-layer lining, however, its failure characteristics and synergistic load-bearing mechanisms under high geo-stress are still unclear. To fill the gap, three-dimensional geomechanical model tests were conducted and synergistic mechanisms were analysed in this study. The model test was divided into normal loading, excavating, and overloading stages. The surrounding rock deformation was monitored by using an improved high-precise extensometer measurement system. Results show that the largest radial deformation appears on the sidewall, followed by the floor and vault during the excavating stage. The relative convergence deformation of sidewalls springing reaches 1.32 mm. The failure characteristics of the multi-layer linings during the overloading stage undergo an evolution of stability, crack initiation, local failure, and collapse, with a safety factor of 1.0–1.6, 1.6–2.0, and 2.0–2.2, respectively. The synergistic load-bearing mechanism analysis results suggest that the early stiffness and late yielding deformation capacity of large deformation support measures play important roles in stability maintenance both in the construction and operation of deep soft rock tunnels. Therefore, the combination of yielding support or a compressible layer with reinforced support is recommended to mitigate the effect of the high geo-stress.